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10th Meeting of the Mediterranean Group for the Study of Diabetes Istanbul – April 26-29, 2007

10th Meeting of the Mediterranean Group for the Study of Diabetes Istanbul – April 26-29, 2007. Lung dysfunctions in Metabolic Syndrome and Diabetes Prof. A. Tiengo University of Padova (Italy). Lazar M. Nat Med 2006. Sleep Disorders-Metabolic Syndrome. Sleep Fragmentation.

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10th Meeting of the Mediterranean Group for the Study of Diabetes Istanbul – April 26-29, 2007

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  1. 10th Meeting of the Mediterranean Group for the Study of DiabetesIstanbul – April 26-29, 2007 Lung dysfunctions in Metabolic Syndrome and Diabetes Prof. A. Tiengo University of Padova (Italy)

  2. Lazar M. Nat Med 2006

  3. Sleep Disorders-Metabolic Syndrome Sleep Fragmentation Sleep Deprivation Intermittent Hypoxemia Sleep Disorders/SDB Metabolic Syndrome Increased Sympathetic Drive

  4. Co-Aggregation of Features of Metabolic Syndrome and SDB • 2/3's OSA patients are obese • 2/3's obese patients have OSA • O.R. = 4-10 • Central / "android" obesity • neck size / waist circumference • 2/3’s OSA patients HTN • High prevalence of hyperlipidemia

  5. Correlation between visceral fat and indices of apnea. , sleep apneics, , obese control Vgonzas et al., Sleep Med Rew, 2005

  6. Obstructive sleep apnoea syndrome and insulin sensitivity ISI composite, hepatic ISI and Δl30-0/ΔG30-0 in normal subjects (NS) obese patients (OB) and obese patients with obstructive sleep apnoea syndrome (OSAS) Tassone et al. Clin Endocrinol, 59, 374, 2003

  7. Adjusted mean value of HOMA index as a function of the respiratory disturbance index (RDI) for 12-month (n=1,067) and 3-month (n=405) time windows. Sleep Heart Health Study, 1994-1999. Punjabi et al, Am J Epidemiol 2004

  8. Adjusted mean value of HOMA index according to two different indices of sleep-related hypoxemia (12-month time windows; n=1,067) Sleep Heart Health Study, 1994-1999. Punjabi et al, Am J Epidemiol 2004

  9. Prevalence of obstructive sleep apnea and excessive daytime sleepiness (EDS) in women with the polycystic ovary syndrome Vgonzas et al., Sleep Med Rew, 2005

  10. Cleveland Family Data • OSA (+) associated with increasing: • IL6/sIL6 • CRP • D-dimer • Fibrinogen • PAI-1 • Leptin • Urinary Microalbumin • Fasting Insulin/Glucose • Not or (-) associated with: • TNFa • MPO

  11. Biochemical Perturbations with Sleep Disorders/SDB • SDB • Increased IGF-1 • Increased insulin • Increased am cortisol • Inflammatory cytokines • Sleep deprivation • Increased cortisol • Decreased growth hormone and thyrotropin • Decreased glucose intolerance

  12. A heuristic model of the complex feed forward associations between visceral fat/insulin resistance, inflammatory cytokines, stress hormones, excessive daytime sleepiness and fatigue, and sleep apnea Vgonzas et al., Sleep Med Rew, 2005

  13. Odds Ratios for prevalent, physician-diagnosed diabetes for two levels of sleep-disordered breathing AHI = apnea-hypopnea index Reichmuth et al., Am J Respir Crit Care Med 2005

  14. Odds Ratios for 4 years incidence of physician-diagnosed diabetes for two levels of sleep-disordered breathing AHI = apnea-hypopnea index Reichmuth et al., Am J Respir Crit Care Med 2005

  15. Fasting Glucose and Hypoxemia Adjusted* Odds Ratio for Impaired or Diabetic Fasting Glucose *Adjusted for age, gender, race, BMI, waist circumference, cohort,smoking

  16. Nine-year adjusted hazard ratios (HR) for incidence for forced vital capacity (FVC) (% predicted) quartile, sex and smoking status Yeh et al., Diabetes Care 2005

  17. Insulin Resistance and Hypoxemia HOMA Index

  18. Spiegel, K. et al. J Appl Physiol 99: 2008-2019 2005;

  19. Mean hemoglobin A1c (HbA1c) levels before and after continuous positive airway pressure (CPAP) treatment in the entire study population and patients with a baseline HbA1c level greater than 7% Babu, A. R. et al. Arch Intern Med 2005;165:447-452.

  20. Number of glucose values greater than 200 mg/dL (11.1 mmol/L) before and after continuous positive airway pressure (CPAP) treatment for the entire study population and patients with an initial hemoglobin A1c (HbA1c) level greater than 7% Babu, A. R. et al. Arch Intern Med 2005;165:447-452.

  21. Association between various clinical definition of diabetes and forced expiratory volume in 1 second, Third National Health and Nutrition Examination Survey, 1988-1994 Model 1 with additional adjustment for BMI and W/H ratio Model 1 McKeever et al, Am J Epidemiol 2005

  22. Association between known diagnosis of diabetes and forced exiratory volume in 1 second, Third National Health and Nutrition Examination Survey, 1988-1994 Model 1 with additional adjustment for BMI and W/H ratio Model 1 McKeever et al, Am J Epidemiol 2005

  23. Association between glycemic state and lung function Relationship of residual FEV1 to level of fasting glucose. Quartiles of blood glucose: first quartile, 48–88 mg/dl; second quartile, 89–94 mg/dl; third quartile, 95–101 mg/dl; and fourth quartile, 102–305 mg/dl; p values are for linear trend across quartiles. Error bars are SDs. Walter Am.J.Respir. Crit. Care Med. 2003:916

  24. Association between glycemic state and lung function Relationship of residual FVC to level of fasting glucose. Quartiles of blood glucose: first quartile, 48–88 mg/dl; second quartile, 89–94 mg/dl; third quartile, 95–101 mg/dl; and fourth quartile, 102–305 mg/dl; p values are for linear trend across quartiles. Error bars are SDs Walter Am.J.Respir. Crit. Care Med. 2003:916

  25. Association between glycemic state and lung function Relationship of residual FEV1/FVC to level of fasting glucose. Quartiles of blood glucose: first quartile, 48–88 mg/dl; second quartile, 89–94 mg/dl; third quartile, 95–101 mg/dl; and fourth quartile , 102–305 mg/dl; p values are for linear trend across quartiles. Walter Am.J.Respir. Crit. Care Med. 2003:916

  26. * *p<0.001 compared to control group and predicted value Reduced vital capacity in insulin-dependent Diabetes Primhak, Diabetes 36: 324-26, 1987

  27. CARDIOVASCULAR DISEASE DIABETES RAISED CHOLESTEROL Dieta SLEEP APNEA HYPERTENSION MORBID OBESITY

  28. Syndrome Z Hypertension Dyslipidemia Sleep Apnea Obesity Insulin Resistance Susceptibility genes forming a common soil

  29. Conclusions • Sleep disordered breathing is a prevalent condition associated with significant comorbidities including obesity, diabetes, hypertension, insulin-resistance and cardiovascular diseases. • The severity of insulin-resistance is related to the severity of sleep disordered breathing. • The hypoxemia and the sleep disorderes breathing may favour the incidence of diabetes. • Diabetic condition and the degree of poorly glycemic control induce an impairment of lung functions.

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